Frontotemporal dementia (FTD) is a common cause of dementia in people under the age of 65 years. Pathologic causes of FTLD may be categorized according to the main pathologic inclusion protein, and the majority of FTLD cases are either FTLD with inclusions immunoreactive to TAR DNA binding protein of 43 kD (FTLD-TDP) or FTLD with inclusions immunoreactive to Tau (FTLD-Tau). The clinical prediction of underlying FTLD pathology based on clinical features, neuropsychological testing, or imaging patterns has been less than optimal, especially in patients with prominent behavioral changes who represent the largest FTLD syndromic group. The poor prediction of underlying FTLD pathology has also significantly hindered the progress in clinical trial design in FTLD, as therapies targeting TDP or Tau cannot be reliably given to patients with the corresponding pathology. Thus, there is a need to improve diagnosis of FTLD subtypes.
Cerebrospinal fluid (CSF) levels of total-tau and phosphorylated-tau have been assessed for certain neurodegenerative diseases. See Grossman et al., Annals of Neurology, 2005, 57(5):721-729. See also Hu et al., Neurology, 2010, 75(23):2079-2086 and Riemenschneider et al., Mol Psychiatry., 2003, 8(3):343-7. An association of total tau and phosphorylated tau 181 protein levels in cerebrospinal fluid has been reported with cerebral atrophy in mild cognitive impairment and Alzheimer disease. See Thomann et al., J Psychiatry Neurosci., 2009, 34(2):136-142. The differential diagnosis of a tauopathy versus a non-tauopathy based on the detection of the ratio of phospho-tau (181)/total tau is reported in U.S. Pat. Nos. 6,680,173 and 7,387,879.